Retroviral vectors, based on Mo-MuLV, are successfully being used as a gene delivery system, for gene transfer into mammalian cells, while host range is determined by the viral envelope glycoprotein gp-70. Although the viral envelope is species specific (ecotropic type, amphotropic type or xenotropic type), it is not tissue specific, and it's host cell range is limited. We are trying to change the Mo-Mulv envelope glycoprotein, in order to target the virus particle (containing recombinant vector) to specific cells, and/or to increase target cell range. Several approaches are being employed: 1. Identification and modification of the viral receptor-recognition site, which is located in the viral envelope glycoprotein - the gp-70. We have demonstrated that by exchanging specific DNA sequences of the viral gp-70, between ecotropic and amphotropic types of Mo-MuLV, host range of these retroviral packages can be interconverted. 2. A large switch is being made, between the Mo-Mulv gp-70 (and part of the gp-15), and the other membrane domain of the influenza virus binding and fusion envelop glycoprotein - the HA. This may allow targeting of retroviral vectors to any mammalian cells having on their surface gangliosides carrying N-acetyl sialic acid. We have demonstrated that chimeric protein can be detected on the producer cells surface and can induce binding and fusion of red blood cells. 3. An attempt is being made to target the virus to specific tissue, by covalently binding of ligands to the virus surface.